Cherin Tony, Catbagan Maria, Treiman Stephen, Mink Richard
Department of Pediatrics, Division of Pediatric Critical Care, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Neurol Res. 2006 Dec;28(8):831-6. doi: 10.1179/016164105X49229.
Cerebral hypoxia-ischemia leads to the depletion of ATP. Hypoxanthine, a degradation product of ATP, can be salvaged by hypoxanthine phosphoribosyl transferase (HPRT) and used to reform high-energy purines. Hypothermia conserves ATP in hypoxia-ischemia, possibly by preserving HPRT activity. We hypothesized that cerebral hypoxia-ischemia would decrease the activity of this enzyme, and that this reduction would be attenuated by moderate hypothermia.
Three groups of rabbits were evaluated. Normothermic rabbits were exposed to 8 minutes of hypoxia, 8 minutes of cerebral ischemia, and 30 minutes or 4 hours of cerebral reperfusion. Hypothermic rabbits were cooled to a brain temperature of 33-34 degrees C throughout identical injury and reperfusion periods. Control rabbits underwent the same preparation, without hypothermia or injury. HPRT activity in the cortex, hippocampus, thalamus, caudate, and cerebellum was measured spectrophotometrically.
There were no significant differences (p>0.05) in enzymatic activity when comparing the three groups of animals, regardless of reperfusion time or brain temperature. Within the control group, some regional differences in enzyme activity were noted.
The results indicate that brain HPRT activity is unaffected by hypoxia-ischemia, even after 4 hours of reperfusion and regardless of brain temperature. This study supports the importance of this enzyme in the conservation of brain purines after neurologic injury.
脑缺氧缺血会导致三磷酸腺苷（ATP）耗竭。次黄嘌呤作为ATP的降解产物，可被次黄嘌呤磷酸核糖转移酶（HPRT）挽救，并用于重新合成高能嘌呤。低温可能通过保留HPRT活性来在缺氧缺血时保存ATP。我们推测脑缺氧缺血会降低该酶的活性，且这种降低会被中度低温所减轻。
评估三组兔子。正常体温的兔子经历8分钟缺氧、8分钟脑缺血以及30分钟或4小时的脑再灌注。低温组兔子在相同的损伤和再灌注期间将脑温冷却至33 - 34摄氏度。对照组兔子进行相同的准备，但不进行低温处理或损伤。通过分光光度法测量皮质、海马、丘脑、尾状核和小脑中的HPRT活性。
比较三组动物时，无论再灌注时间或脑温如何，酶活性均无显著差异（p>0.05）。在对照组内，注意到酶活性存在一些区域差异。
结果表明，即使在4小时再灌注后且无论脑温如何，脑HPRT活性均不受缺氧缺血影响。本研究支持了该酶在神经损伤后脑嘌呤保存中的重要性。
